Study Finds Link between First-line Tenofovir (Viread) Use and Kidney
with HIV have been shown to
have higher rates of kidney
disease. In some cases, this is related to HIV infection itself
(HIV-associated nephropathy), but antiretroviral
drugs may also play a role.
The nucleotide reverse transcriptase inhibitor tenofovir
is eliminated by the kidneys and may accumulate in the proximal
tubules, which maintain metabolic balance (e.g., stable pH) as
the kidneys filter the blood.
In the pivotal clinical trial that led to its approval, tenofovir
was not associated with kidney problems, but those studies excluded
people with pre-existing kidney disease. Studies of "real
world" populations have yielded conflicting data, with some
showing no association and others showing increased risk in susceptible
shed further light on this issue, Michael Horberg from Kaiser
Permanente in Oakland, CA, and colleagues designed a study to
characterize the long-term effects of tenofovir on kidney function
in a large managed care organization.
This retrospective cohort analysis looked at medical records from
treatment-naive HIV positive Kaiser Permanente members who started
antiretroviral therapy during 2002-2005. The study compared 964
patients who started regimens containing tenofovir and 683 who
started tenofovir-sparing regimens.
Baseline characteristics were similar overall, though tenofovir
recipients were more likely to have hepatitis B coinfection (tenofovir
is active against hepatitis B virus as well as HIV). Very few
patients used the older protease inhibitor indinavir
(Crixivan), which has also been linked to kidney dysfunction.
The researchers evaluated multiple measures of kidney function,
including glomerular filtration rate (GFR) using the Modification
of Diet in Renal Disease (MDRD) equation, serum creatinine level,
and development of renal proximal tubular dysfunction over a 2-year
They used multivariate models to adjust for confounding factors
including age, sex, race (blacks are known to have a higher risk
for HIV-associated nephropathy), history of diabetes, hypertension
(high blood pressure), malignancy, hepatitis, concurrent medications,
and baseline laboratory values including CD4 cell count.
5% of patients taking tenofovir experienced a GFR decline
of 50% or more, compared with 3% of patients on tenofovir-sparing
regimens (P = 0.03).
taking tenofovir had a significantly larger relative decline
in GFR through 104 weeks than those on tenofovir-sparing regimens
(-7.6 mL/min/1.73 m(2); P < 0.001).
the degree of difference varied according to baseline GFR,
with the greatest effect seen in patients with initial GFR
> 80 mL/min/1.73 m(2).
recipients had significantly higher serum creatinine levels
at 52 and 104 weeks (both P < 0.001).
controlling for other factors, tenofovir recipients were significantly
more likely to develop proximal tubular dysfunction over time:
hazard ratio (HR) 1.95, or about twice the risk, at
52 weeks (P = 0.01);
HR 5.23, or more than 5-fold higher risk, at 104 weeks
(P = 0.0004).
taking tenofovir also had a greater risk of drug discontinuation
(adjusted HR 1.21; P = 0.02), especially as kidney function
suppression and changes in CD4 count were similar between
the 2 groups.
Based on these findings, the study authors concluded, "Tenofovir
is associated with greater effect on decline in renal function
and a higher risk of proximal tubular dysfunction in antiretroviral
naive patients initiating antiretroviral therapy."
"Given the current commitment to long-term, even life-long
antiretroviral therapy, incremental small annual declines in kidney
function could eventually lead to kidney failure and increased
mortality," they continued in their discussion.
conclude that although efficacious, the potential long-term adverse
effects on kidney function may limit the use of tenofovir for
patients at high risk of renal complications," they summarized.
"Long-term monitoring of renal function and the components
of proximal tubular dysfunction in patients taking tenofovir should
Initiative, Kaiser Permanente, Oakland, CA.
M Horberg, B Tang, W Towner, and others. Impact of tenofovir on
renal function in HIV-infected, antiretroviral-naive patients.
Journal of Acquired Immune Deficiency Syndromes 53(1):